Picture an infant brain as a large, bustling town made up of thousands of neural cells that are constantly on the move, growing, dividing, pushing and pulling to reach their right place. Just as the physical forces shape buildings and roads in cities, the process of brain development involves mechanical forces which influence how the neural cells develop and arrange themselves in different places.
The interaction of fluid pressure, cell tension, rigidity of tissues and movement of cells produces information about the nature of development. The above-mentioned process is a great concern of mechanobiology, which studies how cells are able to sense and react to mechanical forces (Abuwarda & Pathak, 2020).
For decades, researchers have explained the development of the brain primarily through genetics and chemical signalling. Current research shows, however, that the effects of the physical environment are just as important. Mechanotransduction is the process through which cells use mechanical information to produce biological changes capable of influencing growth, gene expression, differentiation, and movement.
Mechanical signals are capable of altering neural stem cells, guiding neuronal migration, and contributing to the formation of complex brain structures (Franze et al., 2013). From this, it follows that the brain undergoing development is not already embedded within biological constraints; instead, this process is ongoing and dependent on the continuous interaction between cells and their physical environment.
Tissue Stiffness and Neural Stem Cell Development
One of the key physical properties influencing the development of the brain is the stiffness of the tissue. Despite the fact that the brain is soft tissue, the mechanical properties of different regions of the brain may differ and change as the brain develops. Stem neural cells are capable of discriminating between different tissue stiffness and making decisions about whether to continue mitosis or move towards the process of specialisation. Some research has revealed that the changes in mechanical properties are taken into consideration also through interaction of cells with the extracellular matrix (Franze et al., 2013).
Neural stem cells detect mechanical stimuli through different structures, including integrins, focal adhesions and the cytoskeleton. This means that neural stem cells can produce tiny pulling forces and analyse the surrounding environment regarding its physical nature. For example, the presence of mechanical stimuli activates some intracellular pathways that affect the behaviour and development of cells (Abuwarda & Pathak, 2020). Mechanosensitive ion channels and molecular pathways can be responsible for converting physical pressure or stretching into a biological response. Mechanical stimuli can change tissue stiffness. Additionally, genetic and chemical factors influence the development and differentiation of neural stem cells. Therefore, all these factors play an important role in neural development (Franze et al., 2013).
When the environment changes, the significance of tissue mechanics becomes evident. A neural cell growing in an unexpectedly stiff or different environment has a different behaviour from that found in normal brain tissue. Variations in the environment influence cell attachment, migration, and differentiation. For this reason, scientists have started studying how synthetic materials with different hardnesses affect neural cells in the lab. This new branch of study might help scientists better understand the role of the physical environment in normal and lethal brain development (Pillai & Franze, 2024).
Pressure, Tension, and Neuronal Migration
Mechanical forces come into play from the initial phases of the development of the nervous system. During the development of the neural tube, cells undergo shape changes and generate tension with the help of the actomyosin cytoskeleton. These precise movements allow the neural tissue to fold and close as required. Mechanical forces generated by cells play an important role in tissue formation. Moreover, these forces influence tissue development during the early stages of development. If these processes are interrupted, the nervous system will be formed incorrectly.
Another factor responsible for brain development is pressure in the changing brain. Ventricles, which are cavities characterised by the presence of liquid, introduce pressure that has potential effects on neural stem and progenitor cells. According to the changes in pressure in the ventricles, there may be an effect on the growth process of the tissue in the brain.
Fluid movement can also create shear forces. These forces act on mechanosensitive elements within cells and may influence their responses (Abuwarda & Pathak, 2020). Brain development is influenced by biological molecules. However, it also responds to physical forces, such as pressure and fluid movement.
Neuronal migration is another developmental process that is influenced by mechanical forces. Neurons that were recently formed are required to move away from the area where they were created to specific spots inside the future brain. As newly formed neurons migrate from one location to another, they interact with neighbouring cells and the extracellular matrix. As a result, they generate traction forces that help propel them forward. Resistance from the surrounding tissues and their stiffness can have an impact on the speed and direction of migration (Franze et al., 2013). Research results show that the migrating cells respond to mechanical characteristics in their surrounding environment (Abuwarda & Pathak, 2020).
Mechanical Forces, Brain Structure, and Neurological Disorders
Mechanical forces influence the brain throughout life. These forces continue to shape neuronal connections and may contribute to the development of neurological disorders (Franze et al., 2013).
- Neuronal development and connectivity: Physical stimuli, including stiffness, tension, and resistance, play a role in axon and dendrite growth, and are thus important in the creation of links among neurons and in the formation of neural networks (Franze, 2013; Franze et al., 2013).
- Brain composition and cortical folding: The growth rate of tissues, pressure levels, and mechanical forces influence the folding of the cerebral cortex and the structure of the brain overall (Bayly et al., 2014; Borrell, 2019).
- Abnormal brain growth: Disturbances in mechanical operations may hinder neuronal migration, thereby influencing cortical organisation. This can contribute to the development of neurological and psychiatric disorders (Monuki & Walsh, 2015).
- Brain tumours and tissue motion: Variations in the properties of tissues and in the extracellular environment may determine how tumours grow, move, and behave, particularly gliomas (Franze et al., 2013).
- Prospects: Learning more about mechanobiology through techniques such as brain organoids, cutting-edge imaging, and biomaterials can lead to a better understanding of brain disorders and the development of innovative treatments (Abuwarda & Pathak, 2020).
By understanding how an organism’s mechanical environment impacts brain properties, we can gain insights into the brain’s development and dysfunction. As mechanobiology advances, scientists can gain a better understanding of the mechanisms behind neurological diseases. Furthermore, these findings may help improve the diagnosis and treatment of these diseases (Bayly et al., 2018; Franze et al., 2013).
Conclusion
Brain development results from both genetic factors and chemical/physical factors. Tissue stiffness, pressure, and tension are important physical factors. In addition, fluid movement and cellular traction may also provide crucial information. These factors can influence neural stem cells and neurons as they develop. Mechanotransduction is how cells convert these physical signals into biological responses that define proliferation, differentiation, migration and neuronal growth.
Mechanical forces represent a new view on the establishment of the nervous system and nervous system diseases. Understanding how cells react to their physical environment is important. Moreover, it can improve our understanding of developmental conditions and neuropathologies, such as brain tumours (Pillai & Franze, 2024). Additionally, there are possibilities for new applications of these findings in techniques for modelling the brain and regenerative medicine. Ultimately, genes do not shape the brain alone.
References +
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